Umbrella Cells Mimicking Focal High-Grade Urothelial Carcinoma in Low-Grade Papillary Urothelial Carcinoma

2019 ◽  
Vol 152 (Supplement_1) ◽  
pp. S121-S121
Author(s):  
Muhammad Masood Hassan ◽  
Tammey Naab ◽  
Ali Afsari

Abstract Objectives Low-grade papillary urothelial carcinoma (LGUC) has overall a preserved orderly appearance, minimal variability in architecture, and lack of significant cytologic atypia and mitotic activity without pleomorphism. A total of 53.8% of LGUC cases recur with 18.3% progression to high-grade UC. Even focal HGUC in LGUC can be a harbinger of progression. Accurate pathological interpretation is paramount in predicting recurrence and determining treatment. Methods A 63-year-old male with a past medical history of coronary artery disease, benign prostate hyperplasia, and obesity was referred to urology with a chief complaint of chronic hematuria. Cystoscopy with transurethral resection of bladder tumor was performed, which revealed mainly LGUC with focal high-grade-appearing UC. Results Histologic sections revealed papillary architecture with fused fronds, low-grade nuclear atypia, and scattered mitoses comprising 95% of the tissue submitted. No muscular wall invasion by carcinoma was seen. However, in one section, collections of large cells with well-defined cytoplasmic borders, multinucleation, and rare nuclear grooves were identified. The morphology raised the suspicion of a focal HGUC. Diffuse expression of CK20 and low Ki-67 proliferation index (1%) favored umbrella cells. Conclusion Our case reinforces the fact that sectioning can reveal foci, suspicious for HGUC, especially in urothelium. However, proper interpretation of morphology combined with the help of immunohistochemistry aids in accurate diagnosis, which is critical in determining proper clinical management of the patient.

2008 ◽  
Vol 132 (2) ◽  
pp. 224-231
Author(s):  
Ying-bei Chen ◽  
Jiangling J. Tu ◽  
Jean Kao ◽  
Xi K. Zhou ◽  
Yao-Tseng Chen

Abstract Context.—Distinguishing low-grade and high-grade noninvasive papillary urothelial carcinoma based on morphologic criteria can be challenging and adjunct markers are highly desirable. Survivin, presumably an antiapoptotic protein, was previously proposed as a prognostic marker for urothelial carcinoma. Objective.—To assess interobserver variability by 2004 World Health Organization classification and the value of survivin and Ki-67 as potential markers for grading noninvasive papillary urothelial carcinoma. Design.—Fifty-one bladder biopsies were graded blindly by 5 experienced general surgical pathologists. The protein and messenger RNA expression of survivin and Ki-67 was evaluated by immunohistochemistry and quantitative reverse transcription–polymerase chain reaction using paraffin-embedded tissue. The immunohistochemistry result was quantitatively analyzed using a computer-based color deconvolution module. Results.—The diagnostic agreement among 5 pathologists was fair to poor, with 32% of the cases graded differently by at least 2 raters. All cases were divided into 3 groups: consensus low-grade, consensus high-grade, and indeterminate. The percentage of urothelial cells with positive survivin nuclear staining (survivin score) was significantly higher in the high-grade than in the low-grade group (P < .001). Survivin score outperformed Ki-67 in separating the high-grade group from the low-grade group and showed a significantly higher predictive accuracy for high-grade recurrence than the histologic grade. The disagreement of grading for the indeterminate group could be resolved by their survivin scores in most cases. Survivin messenger RNA level correlated well with survivin score by immunohistochemistry but was not a more discriminating marker. Conclusions—Significant interobserver variability exists in grading low-grade versus high-grade papillary urothelial carcinoma. Survivin immunohistochemical staining can be a useful adjunct tool for the grading of challenging cases.


2021 ◽  
Vol 8 (9) ◽  
pp. 497-501
Author(s):  
Sebina Asmi A.T ◽  
Suma Madathiveetil

BACKGROUND Human epidermal growth factor receptor-2 HER2 / neu, is a trans membrane tyrosine kinase receptor of epidermal growth factor receptor (EGFR) family and is involved in the pathogenesis of urinary bladder cancer. In this study we attempted to evaluate the HER2 / neu expression in urothelial carcinoma of bladder and its association with tumour grading. METHODS This was a cross sectional study with a sample size of 75. Routine 4 micrometre thick sections of formalin fixed paraffin embedded tissue blocks stained with haematoxylin & eosin were reviewed. Tumour grade was determined by using the World Health Organization (WHO) / International Society of Urological Pathologist criteria (ISUP). Immunohistochemistry was done by using HER2 / neu monoclonal antibody and its expression were observed. The membrane staining intensity and pattern were studied and scored. RESULTS In our study 75 cases of urothelial carcinoma were studied, of which 49 cases were papillary urothelial carcinoma low grade, 26 cases were papillary urothelial carcinoma high grade. Among these, 19 cases were infiltrating urothelial carcinoma. HER2 / neu positivity were observed in 27 (36 %) cases and overexpression in 8 (10 %) cases. Low grade urothelial carcinoma showed HER2 / neu positivity in 11 (22 %) cases and overexpression in 1 (2 %) case. High grade urothelial carcinoma showed HER2 / neu positivity in 16 (64 %) cases, among which 7 (28 %) cases showed overexpression. HER2 / neu positivity was seen in 13 (68 %) cases of infiltrating urothelial carcinoma with 4 (21 %) cases showing overexpression. A statistically significant difference in HER2 / neu expression was noted in high grade and invasive urothelial carcinoma compared to low grade and non-invasive urothelial carcinoma. CONCLUSIONS Urothelial carcinomas show overexpression of HER2 / neu and this over expression increases with increasing grade of tumour and muscle invasiveness. KEYWORDS Urothelial Carcinoma, HER2 / neu, Overexpression, Tumour Grade, Trastuzumab


2021 ◽  
pp. 106689692110522
Author(s):  
Diego Montoya-Cerrillo ◽  
Laurence M. Briski ◽  
Merce Jorda ◽  
Oleksandr N. Kryvenko

Background Condyloma acuminatum is a squamous epithelial lesion which uncommonly involves the urinary tract. In this location, non-invasive papillary urothelial carcinoma constitutes one of the main differential diagnoses with significant prognostic and therapeutic implications. To date, no ancillary immunohistochemical stain has been described to differentiate these two entities. We assess the utility of cytokeratin 5/6 (CK5/6) and GATA-3 immunohistochemistry in distinguishing condyloma acuminatum from non-invasive papillary urothelial carcinoma. Design We reviewed 9 condylomata acuminata involving the urinary tract, 12 low-grade and 8 high-grade non-invasive papillary urothelial carcinomas. CK5/6 immunostaining was performed in all cases. GATA-3 immunostaining and low-risk human papilloma virus (HPV) chromogenic in situ hybridization was performed in all condyloma cases and 2 urothelial carcinomas with squamous differentiation. Results 8/9 condylomata acuminata were positive for low-risk HPV. All condylomata acuminata exhibited strong full-thickness cytoplasmic staining for CK5/6. In 10 of 12 low-grade non-invasive papillary urothelial carcinomas, CK5/6 expression was continuous and limited to the basal cell layer, while it was patchy and limited to the basal cell layer in all 8 high-grade non-invasive papillary urothelial carcinomas. Two low-grade non-invasive papillary urothelial carcinomas showed focal full-thickness CK5/6 expression in the areas of squamous differentiation. These 2 cases were negative for low-risk HPV. GATA-3 immunostaining was positive in all condylomata acuminata. Conclusions CK5/6 immunostaining is a useful and simple tool that can help separate low-grade and high-grade non-invasive papillary urothelial carcinomas from condyloma acuminatum involving the urothelium-lined organs. GATA-3 has no discriminatory role between condyloma acuminatum and papillary urothelial carcinomas.


2014 ◽  
Vol 138 (9) ◽  
pp. 1215-1222 ◽  
Author(s):  
Maria E. Vergara-Lluri ◽  
Eugenia Hu ◽  
Jian-Yu Rao ◽  
Mary Levin ◽  
Sophia K. Apple ◽  
...  

Context.—Detection of urothelial carcinoma by urine cytology can be challenging. Recently, ProEx C has been studied as a marker to improve detection of urothelial carcinoma. ProEx C is an assay targeting expression of topoisomerase II-α and the minichromosome maintenance protein-2 and is used to assist in diagnoses of gynecologic specimens. Objective.—To evaluate the utility of ProEx C and uCyt in atypical urine cytology. Design.—Sixty-eight specimens with a diagnosis of atypical urine cytology, concurrent uCyt testing, and surgical biopsy follow-up were included. Slides were restained with ProEx C. ProEx C was recorded as positive when nuclear staining was seen in at least one morphologically atypical urothelial cell. The uCyt was scored as positive if at least one morphologically atypical urothelial cell showed positive fluorescence staining. Thirteen cases (19%) had benign histologic diagnoses, 18 (26%) had low-grade papillary urothelial carcinoma, and 37 (54%) had high-grade urothelial carcinoma. Results.—The overall sensitivity was 85% for ProEx C, 85% for uCyt, and 93% for the combination of the 2 assays. The overall specificity was 69% for ProEx C, 31% for uCyt, and 23% for the combination of the 2 tests. In predicting high-grade urothelial carcinoma, sensitivity was 92% for ProEx C, 86% for uCyt, and 92% for both tests. In predicting low-grade papillary urothelial carcinoma, sensitivity was best with the combination of the 2 tests at 94%. Conclusion.—ProEx C has superior specificity to uCyt. The combination of the 2 tests yielded high sensitivity not only for high-grade urothelial carcinoma but also for low-grade papillary urothelial carcinoma.


2020 ◽  
pp. 1-4
Author(s):  
Nishat Ahmad ◽  
Saurabh Banerjee ◽  
A K. Srivastava

BACKGROUND: Urinary bladder cancer is second most common cancer after prostate cancer in the genitourinary system. Urothelial Carcinoma is the commonest tumour type accounting for 90% of all primary tumours of the bladder Histopathological analysis of cystoscopic bladder biopsy and Transurethral resection of the bladder tumour (TURBT) material are the mainstay for cancer diagnosis. This study was aimed to determine the frequency of different types of neoplastic lesions of the urinary bladder and to determine the grade and stage of urothelial tumours. MATERIAL METHOD: The study was carried out in the Department of Pathology, Rajendra Institute of Medical Sciences (RIMS), Ranchi from January 2018 to June 2020 and included 30 cases of cystoscopic biopsies and TURBT specimens. RESULTS: Out of 30 cases of neoplastic lesions, majority were of high grade papillary urothelial carcinoma (n=14, 46.67%) followed by low grade papillary urothelial carcinoma (n=9, 30%), 3 cases (10%) were of PUNLMP, 2 cases (6.66%) of papilloma and 1 (3.33%) case each of moderately differentiated squamous cell carcinoma and extra nodal NHL. The most common age group was 41-50 years and 51-60 years with 9 (30%) cases each. Muscle invasion was seen only in high grade papillary urothelial carcinomas. CONCLUSION: High-grade urothelial carcinomas with lamina propria and muscle invasion are the most common neoplastic lesion of urinary bladder with significant morbidity and mortality. Muscle invasion and grading, as per TNM staging, are valuable prognostic factors.


2010 ◽  
Vol 134 (8) ◽  
pp. 1160-1163
Author(s):  
Hiroshi Miyamoto ◽  
Fadi Brimo ◽  
Luciana Schultz ◽  
Huihui Ye ◽  
Jeremy S. Miller ◽  
...  

Abstract Context.—Few large cohort studies have addressed outcome in patients with noninvasive low-grade papillary urothelial carcinoma (LG-UrCa) following implementation of the 2004 World Health Organization/International Society of Urological Pathology (WHO/ISUP) consensus classification. Objective.—To evaluate our cohort of LG-UrCa cases classified according to 2004 WHO/ISUP to reassess outcome and interobserver agreement. Design.—Files were searched for all patients diagnosed with LG-UrCa between 1998 and 2008. All sections were reevaluated for accuracy of classification. Results.—A total of 112 cases initially diagnosed as LG-UrCa were identified. Of those, 8 of 55 cases (15%) initially diagnosed by nonurologic pathologists were reclassified as high-grade papillary urothelial carcinoma and were excluded. The mean length of follow-up was 40.1 months (range, 2–113 months). Tumor recurrence was encountered in 56 of 104 patients (53.8%), including 37 (35.6%) with LG-UrCa or lower-grade tumors and 19 (18.3%) with high-grade papillary urothelial carcinoma. Of the 19 patients demonstrating grade progression, 7 (37%) also developed stage progression (invasive carcinoma, n  =  5; metastatic carcinoma, n  =  2). Seven patients eventually underwent radical cystectomy. None of the 104 patients died of bladder cancer. The mean number of recurrence episodes was 3.11. The mean durations of time to first recurrence and time to grade progression were 13.9 months and 25.1 months, respectively. The mean size of initial tumors was 1.73 cm. There was no significant correlation between tumor size, patient age, sex, or smoking history and the likelihood for recurrence or grade progression. A significantly higher rate of recurrence was seen in patients with multiple tumors at initial diagnosis (P  =  .04). Conclusions.—A tendency to underdiagnose high-grade papillary urothelial carcinoma continues to exist. More than half (53.8%) of patients with LG-UrCa developed recurrence, with an 18.3% incidence of grade progression and a 6.7% incidence of stage progression. Patients with multiple initial tumors had significantly higher risk of developing recurrence.


2020 ◽  
pp. 028418512092214
Author(s):  
Mustafa Bozdağ ◽  
Ali Er ◽  
Sümeyye Ekmekçi

Background Accurate preoperative determination of the histological grade and cellular proliferative potential of meningioma by non-invasive imaging is of paramount importance. Purpose To evaluate the utility of apparent diffusion coefficient (ADC) in determining the histological grade of meningioma, and to investigate the correlation of ADC with Ki-67 proliferation index (PI), progesterone receptor (PR) status, and a number of other histopathological parameters. Material and Methods Histopathologically confirmed 94 meningioma patients (72 low-grade, 22 high-grade) who had undergone preoperative diffusion-weighted imaging were retrospectively evaluated. ADC values were obtained by manually drawing the regions of interest (ROIs) within the solid components of the tumor. The relationship between ADC and Ki-67 values, PR status, and multiple histopathological parameters were investigated, and the ADC values of high-grade and low-grade meningiomas were compared. Independent sample t-test, Mann–Whitney U test, receiver operating characteristic, Pearson correlation, and multiple logistic regression analysis were used for statistical assessment. Results All ADC and rADC values were significantly lower in high-grade meningiomas than in low-grade meningiomas (all P < 0.05). ADC values showed significantly negative correlations with Ki-67 and mitotic index ( P < 0.001 for each). Numerous ADC parameters were significantly lower in meningiomas demonstrating hypercellularity and necrosis features ( P < 0.05). ADC values did not show a significant correlation with PR score (all P > 0.05). Conclusion ADC can be utilized as a reliable imaging biomarker for predicting the proliferative potential and histological grade in meningiomas.


2016 ◽  
Vol 47 (1) ◽  
pp. 20-25 ◽  
Author(s):  
Leonardo O. Reis ◽  
Diana Taheri ◽  
Alcides Chaux ◽  
Gunes Guner ◽  
Maria A. Mendoza Rodriguez ◽  
...  

2021 ◽  
pp. 106689692110324
Author(s):  
Fengming Chen ◽  
Shreyas Joshi ◽  
Bradley C. Carthon ◽  
Adeboye O. Osunkoya

Primary urothelial carcinoma (UCa) of the urethra is relatively uncommon, and the underlying pathogenesis has not been well characterized, especially in the absence of concurrent UCa at other sites. A search for cases of primary UCa of the urethra was conducted. Patients with concurrent UCa of the renal pelvis, ureter, or bladder at the time of diagnosis of the primary tumor were excluded. Clinicopathologic and follow-up data were obtained. A total of 35 cases from 30 patients (27 male and 3 female) were included in the study. The mean patient age at the initial diagnosis was 71 years (range: 41-90 years). Cases were composed of high-grade UCa (26 of 35 = 74%), low-grade UCa (4 of 35 = 11%), and UCa in situ (5 of 35 = 14%). Invasion was present in 14 of 26 (54%) cases of high-grade UCa. Interestingly, 23 of 30 (77%) patients had a previous history of UCa including 7 (30%) cases with divergent differentiation or variant histology. Follow-up data were available in 23 patients with a mean duration of 26.7 months (range: 0.6-87 months). Eleven patients (31%) died of metastatic UCa. This is one of the largest studies to date of primary UCa of the urethra without concurrent UCa of the renal pelvis, ureter, or bladder. Previous history of UCa of the bladder, especially with divergent differentiation or variant histology is conceivably a key risk factor for developing subsequent primary UCa of the urethra. These findings are important for the development of surveillance protocols and therapeutic strategies.


2019 ◽  
Vol 14 (1) ◽  
Author(s):  
Walquiria Quida Salles Pereira Primo ◽  
Guttenberg Rodrigues Pereira Primo ◽  
Dunya Bachour Basilio ◽  
Karime Kalil Machado ◽  
Jesus Paula Carvalho ◽  
...  

Abstract Background Vulvar extramammary Paget disease is a rare chronic condition, that presents with non-specific symptoms such as pruritus and eczematous lesions. Because most of these lesions are noninvasive, the distinction between primary and secondary Paget disease is crucial to management. Case presentation We report an unusual case of vulvar Paget disease associated with massive dermal vascular embolization, cervicovaginal involvement and metastasis to inguinal and retroperitoneal lymph nodes. The intraepithelial vulvar lesion had a classical appearance and was accompanied by extensive component of dermal lymphovascular tumor emboli, similar to those observed in inflammatory breast carcinoma. Immunohistochemical analysis revealed that the lesion was secondary to high-grade urothelial cell carcinoma. The patient had a history of superficial low-grade papillary urothelial carcinoma of the bladder, which had appeared 2 years before the onset of vulvar symptoms. Conclusions Eczematoid vulvar lesions merit careful clinical examination and biopsy, including vulva mapping and immunohistochemistry. The information obtained may help to define and classify a particular presentation of Paget disease. Noninvasive primary lesions do not require the same aggressive approaches required for the treatment of invasive and secondary disease.


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